Thermal stability and decompositions kinetics under non-isothermal conditions of imatinib mesylate α form

Mucha, Igor; Baranowski, P.; Owczarek, Artur; Gajda, Maciej; Pluta, Janusz; Gòrniak, Agata; Niklewicz, Paweł

doi:10.1016/j.jpba.2016.06.032

Cited by 9 publications

(7 citation statements)

References 22 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The studied sample displayed peaks at 2 θ values of 10.38°, 11.17°, 11.89°, 12.11°, 12.85°, 13.78°, 14.82°, 16.42°, 17.62°, 18.02°, 18.53°, 19.03°, 21.19°, 19.75°, 21.19°, 21.55°, 22.56°, 23.12°, 23.66°, 24.83°, 26.24°, 27.33°, 27.93°, 28.46°, and 31.92. The obtained results correspond to α form and literature data [50]. The amorphous sample of the drug stored at 25 °C under controlled relative humidity at different ageing times is shown in Figure 6b–g.…”

Section: Resultssupporting

confidence: 85%

See 1 more Smart Citation

Molecular Mobility and Stability Studies of Amorphous Imatinib Mesylate

2019

Self Cite

View full text Add to dashboard Cite

The proposed study examined the characterization and stability of solid-state amorphous imatinib mesylate (IM) after 15 months under controlled relative humidity (60 ± 5%) and temperature (25 ± 2 °C) conditions. After 2 weeks, and 1, 3, 6, and 15 months, the samples were characterized using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray powder diffractometry (XRPD), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and scanning electron microscopy (SEM). Additionally, the amorphous form of imatinib mesylate was obtained via supercooling of the melt in a DSC apparatus, and aged at various temperatures (3, 15, 25 and 30 °C) and time periods (1–16 h). Glass transition and enthalpy relaxation were used to calculate molecular-relaxation-time parameters. The Kohlrausch–Williams–Watts (KWW) equation was applied to fit the experimental enthalpy-relaxation data. The mean molecular-relaxation-time constant (τ) increased with decreasing ageing temperature. The results showed a high stability of amorphous imatinib mesylate adequate to enable its use in solid dosage form.

show abstract

Section: Resultssupporting

confidence: 85%

“…Our previous studies confirmed that both commercial and synthetized IM occur in crystalline α form [50].…”

Section: Methodssupporting

confidence: 84%

Molecular Mobility and Stability Studies of Amorphous Imatinib Mesylate

2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…In aqueous media, imatinib base is characterized by poor solubility (0.01 mg mL -1 ) [1]. However, the mesylate salt of imatinib, which exists as a polymorph with two principal forms, [2,3] is very soluble in media at pH values B5.5, but in neutral and alkaline aqueous buffers is poorly soluble or insoluble [4]. Therefore, imatinib mesylate belongs to Class 2 of Biopharmaceutical Classification System (BCS) with a solubility of 1 mg mL -1 determined at pH 7.4 [4].…”

Section: Introductionmentioning

confidence: 99%

Pluronic F127 as a suitable carrier for preparing the imatinib base solid dispersions and its potential in development of a modified release dosage forms

Karolewicz

Gajda

Gòrniak

et al. 2017

J Therm Anal Calorim

Self Cite

View full text Add to dashboard Cite

In recent years, considerable attention focuses on making sustained release dosage forms also containing solid dispersions. The objective of this study is evaluation of imatinib base (IMA) solid dispersion physicochemical properties which can be useful to controlled release solid dosage formation. The solid dispersions were obtained by kneading method, containing of 10-90% w/w Pluronic F127 (PLU). Drug dissolution test was determined by rotating-disc system method in 0.1 M hydrochloric acid (pH 1.2) and phosphate buffer (pH 6.8). XRD, DSC, FTIR, and SEM observations were performed to evaluate the physical characteristics of solid dispersions. These studies showed that there was no chemical interaction of the IMA with PLU in the solid state and revealed that IMA and PLU form a simple eutectic phase diagram. Our research has shown that the dynamics of the release of imatinib base from solid dispersions with Pluronic F127 depends on the pH of dissolution medium. At pH 1.2, the presence of polymer in solid dispersion causes delaying of drug release due to formation a viscous gel layer, whereas at pH 6.8 significant enhancement of the drug dissolution rate from solid dispersions has been observed compared to pure IMA. The highest improvement was observed in solid dispersions containing 20 and 30% w/w polymer. The present investigation confirmed that the hydrophilic polymer Pluronic F127 could be applied as a suitable matrix to design modified release formulations of imatinib base.

show abstract

“…Imatinib mesylate (IM), a phenylaminopyrimidine derivate chemically named N‐ {3‐[−4‐(pyridin‐3‐yl)pyrimidin‐2‐ylamino]‐4‐methylphenyl}‐4‐[(4‐methylpiperazin‐1‐yl) methyl]‐benzamide methanesulfonic acid salt, is a tyrosine kinase inhibitor approved for use by the FDA agency in 2001. IM is used for the treatment of gastrointestinal stromal tumors and chronic myeloid leukemia after failure of interferon‐alpha therapy and in pediatric patients whose disease recurred after stem cell transplant (Mucha et al, ; Nageswari, Krishna‐Reddy, & Mukkanti, ). IM was also approved for use after the surgical removal of KIT‐positive tumors to help prevent recurrence (Reddy Arava, Reddy Bethi, Rao Cherukuri, Thota, & Reddy Cherukupally, ).…”

Section: Introductionmentioning

confidence: 99%

Characterization of imatinib mesylate formulations distributed in South American countries: Determination of genotoxic impurities by UHPLC–MS/MS and dissolution profile

Wolff

Dillenburg

Antunes

et al. 2018

Biomedical Chromatography

View full text Add to dashboard Cite

Imatinib mesylate (IM) is an anti-neoplasic drug used for the treatment of cancer. Recent new guidelines specify daily doses and concentration limits for genotoxic impurities (GTIs) in pharmaceutical final products. Therefore, in this work an analytical method using UHPLC-MS/MS was developed, validated and applied to characterize IM tablets for two GTIs: N-(2-methyl-5-aminophenyl)-4-(3-pyridyl)-2-pyrimidine amine (Imp. 1), and N-[4-methyl-3-(4-methyl-3-yl-pyrimidin-2-ylamino)-phenyl]-4- chloromethyl benzamide (Imp. 2), simultaneously. Additionally, dissolution data of IM tablets were compared using a methodology recommended by the US Food and Drug Administration. The UHPLC method utilized an Acquity BEH C (150 × 2.1 mm, 1.7 μm) maintained at 40°C. The mobile phase consisted of ammonium formate 0.063% (phase A) and acetonitrile plus 0.05% formic acid (phase B) in gradient elution. A sensitive method for determination of previously mentioned GTIs in IM tablets was successfully developed and applied. Overall, the formulations analyzed in this work showed low levels of Imp. 1 and Imp. 2. However, the sample named D1 showed very high levels of Imp. 1 and failed to meet the requirements established by the US Food and Drug Administration for dissolution data. Periodic verification of GTIs in pharmaceutical formulations is important to minimize safety risks, so analytical methods to determine it need be available and implemented in routine analysis.

show abstract

Thermal stability and decompositions kinetics under non-isothermal conditions of imatinib mesylate α form

Cited by 9 publications

References 22 publications

Molecular Mobility and Stability Studies of Amorphous Imatinib Mesylate

Molecular Mobility and Stability Studies of Amorphous Imatinib Mesylate

Pluronic F127 as a suitable carrier for preparing the imatinib base solid dispersions and its potential in development of a modified release dosage forms

Characterization of imatinib mesylate formulations distributed in South American countries: Determination of genotoxic impurities by UHPLC–MS/MS and dissolution profile

Contact Info

Product

Resources

About